Aided by a sensitive radioimmunoassay and by improved procedures for extracting oxytocin from plasma, this project will address the question of how the brain exerts neurochemical control over the secretion of peptides for focusing on oxytocin secretion, a steroid-dependent, hypothalamic function readily accessible to direct examination in a physiological context. A pharmacological approach will be used to determine which monoaminergic system in the brain is most critical in mediating oxytocin-releasing stimuli from the vagina. A combination of pharmacological and physiological techniques will be applied to define the role of prostaglandins in the regulation of oxytocin release. The proposal also includes experiments designed to pursue the discovery, made in this laboratory, that oxytocin can act through steroid-dependent, high-affinity receptors in the uterine endometrium to cause endometrial tissue to release large amounts of prostaglandin. A preparation of intact, isolated endometrial cells will be used to characterize the extent to which ovarian steroid hormones regulate the concentration and binding characteristics of the receptors, to correlate oxytocin-binding with prostaglandin production as the biochemical response of the cells to oxytocin, to determine the role, if any, of cyclic nucleotides in the response, and to study the effects of analogues of oxytocin with a view toward identifying peptides of pharmacological value in the control of uterine prostaglandin release in vivo.